title: Formulation and in vivo evaluation of sodium alendronate spray-dried microparticles intended for lung delivery.
abstract: Spray-dried powders for lung delivery of sodium alendronate (SA) were prepared from hydroalcoholic solutions. Formulations display geometric particle size below to 12 μm and spherical shape associated to a hollow structure. The addition of leucine and ammonium bicarbonate leads to porous particles with rough surfaces. The tapped density ranges from 0.016 to 0.062 g/cm(3), decreasing with the increase of the leucine concentration. For all formulations, the calculated aerodynamic diameters are lower than 5 μm. The in vitro aerodynamic evaluation shows that all powders present a high emitted fraction of 100%, a fine particle fraction ranging from 34.4% to 62.0% and an alveolar fraction ranging from to 23.7% to 42.6%. An optimized sample was evaluated regarding sodium alendronate acute pulmonary toxicity and lung bioavailability. The bronchoalveolar lavage study shows that the intratracheal administration of sodium alendronate dry powder and sodium alendronate aqueous solution do not induce significant increases of lung toxicity indicators as compared with the positive control. Moreover, the intratracheal administration of sodium alendronate dry powder results in a 6.23 ± 0.83% bioavailability, a 3.5-fold increase as compared to oral bioavailability. Finally, these results suggest that sodium alendronate pulmonary delivery could be a new and promising administration route.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Curso de Farmácia, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Cruz
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
authors.forename: Leandro
authors.initials: L
authors.lastname: Tasso
authors.forename: Gabrielle C
authors.initials: GC
authors.lastname: Freitas
authors.forename: Adriano B
authors.initials: AB
authors.lastname: Carregaro
authors.forename: Sílvia S
authors.initials: SS
authors.lastname: Guterres
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Pohlmann
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry; D019386:Alendronate / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D000818:Animals; D001639:Bicarbonates / Q000737:chemistry; D001682:Biological Availability; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004285:Dogs; D000431:Ethanol / Q000737:chemistry; D007322:Instillation, Drug; D007327:Insufflation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007930:Leucine / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D010592:Pharmaceutic Aids / Q000737:chemistry; D011208:Powders; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013046:Specific Gravity; D013499:Surface Properties
chemical_list: D000336:Aerosols; D001639:Bicarbonates; D010592:Pharmaceutic Aids; D011208:Powders; D011506:Proteins; D000431:Ethanol; C027043:ammonium bicarbonate; D007770:L-Lactate Dehydrogenase; D007930:Leucine; D019386:Alendronate